Expression of E-cadherin and its relation to the p53 protein status in human breast carcinomas.
In breast carcinomas the TP53 gene is altered in 10-30% of cases. Alteration of the gene may lead to a general genomic instability, detected as deletions and/or amplifications at the gene level, and as altered expression at the mRNA and protein level. We have demonstrated a strong association between down-regulation of E-cadherin protein expression and alterations of the p53 protein, detected as TP53 gene mutation and/or protein accumulation in tumour samples from 210 patients with breast carcinomas (P < 0.001). Investigation of allelic imbalance using microsatellite markers located near the E-cadherin locus was also performed. A higher frequency of loss of heterozygosity in the microsatellite marker closest to the E-cadherin locus was observed in samples with down-regulation of E-cadherin protein expression. A higher frequency of down-regulation of the E-cadherin protein expression was found in invasive lobular carcinomas than in invasive ductal carcinomas, although this difference was of borderline significant (P = 0.084). Cases in the present series were also immunostained for cerB-2 protein overexpression. A significant association between p53 protein accumulation and cerbB-2 protein overexpression was seen (P = 0.036). The results of the present study indicate that p53 protein may play a role in regulation of E-cadherin protein expression.
Bukholm
I K
IK
Department of Genetics, Norwegian Radium Hospital, Oslo, Norway.
Nesland
J M
JM
Kåresen
R
R
Jacobsen
U
U
Børresen-Dale
A L
AL
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D005260:Female; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D007124:Immunoenzyme Techniques; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D008875:Middle Aged; D009154:Mutation; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D015820:Cadherins; D018719:Erb-b2 Receptor Tyrosine Kinases; D016159:Tumor Suppressor Protein p53